PMID- 18375208
OWN - NLM
STAT- MEDLINE
DCOM- 20090129
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1786
IP  - 2
DP  - 2008 Dec
TI  - Predicting the efficacy of trastuzumab-based therapy in breast cancer: current 
      standards and future strategies.
PG  - 105-13
LID - 10.1016/j.bbcan.2008.02.003 [doi]
AB  - Breast cancer is the most common female malignancy in many industrialized 
      countries. Approximately one fourth of all women diagnosed with early breast 
      cancer present with tumors that are characterized by erbB2 amplification. While 
      the associated Her-2/neu receptor overexpression results in a high risk of 
      relapse and poor prognosis, these tumors also represent a target for a selective 
      monoclonal antibody therapy with trastuzumab (Herceptin). The combination of 
      trastuzumab with chemotherapy has led to a considerable reduction of recurrences 
      and to a significant reduction in breast cancer mortality both in the adjuvant 
      and metastatic setting. Unfortunately, despite Her-2/neu overexpression, not all 
      patients equally benefit from trastuzumab treatment, and almost all women with 
      metastatic breast cancer eventually progress during antibody therapy. Moreover, 
      trastuzumab is burdened with cardiotoxicity, thus increasing the risk of 
      symptomatic congestive heart failure. In addition, the marginal costs for a 1 
      year therapy of trastuzumab-based therapy, which is currently considered to be 
      the most effective treatment regimen in the adjuvant setting, may amount for up 
      to US$ 40.000. Testing for erbB2 oncogene amplification by fluorescence in situ 
      hybridization (FISH) and chromogenic in situ hybridization (CISH), respectively, 
      and staining for Her-2/neu receptor overexpression by immunohistochemistry (IHC) 
      represent the current standard for determining patient eligibility for 
      trastuzumab-based therapy. However, while the negative predictive value of these 
      assays for predicting the absence of benefit from trastuzumab-based therapy is 
      sufficiently high, their positive predictive value remains insufficient, i.e. 
      only a proportion of patients selected by these tests substantially benefit from 
      trastuzumab-containing regimen. Accordingly, over the last years a number of 
      biomarkers have been evaluated in their potential to predict response to 
      trastuzumab-based therapies. These include markers auf activation of Her-2/neu 
      (e.g., tyrosine phosphorylated Her-2/neu in tissue and cleaved Her-2/neu 
      extracellular domain in serum) and its dimerization partners (e.g., EGFR), 
      respectively, but also components of Her-2/neu-induced downstream signaling 
      pathways that are crucial for the growth inhibitory effects of trastuzumab (e.g., 
      PTEN and PI3K). Other parameters, such as topoisomerase-II alpha and c-myc 
      co-amplifications, have also been identified as potentially useful predictors of 
      response to trastuzumab-based chemotherapy regimen. While the benefit of these 
      predictive biomarkers in the metastatic setting is currently explored, their 
      usefulness in the adjuvant setting is still largely unknown. It is, however, 
      undisputable that, within the group of Her-2/neu overexpressing tumors, further 
      response predictors are needed in order to minimize trastuzumab-associated side 
      effects, and to reduce the considerable societal costs that are associated with 
      trastuzumab-based treatment regimen.
FAU - Singer, Christian F
AU  - Singer CF
AD  - Division of Special Gynecology, Medical University of Vienna and 
      Ludwig-Boltzmann-Institute of Clinical and Experimental Oncology, Vienna, 
      Austria. christian.singer@meduniwien.ac.at
FAU - Kostler, Wolfgang J
AU  - Kostler WJ
FAU - Hudelist, Gernot
AU  - Hudelist G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20080304
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal/economics/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biomarkers, Tumor/analysis
MH  - Breast Neoplasms/*drug therapy
MH  - Chemotherapy, Adjuvant
MH  - Clinical Trials as Topic
MH  - Female
MH  - Forecasting
MH  - Gene Amplification
MH  - Genes, erbB-2
MH  - Humans
MH  - Models, Biological
MH  - Neoplasm Metastasis
MH  - Receptor, ErbB-2/analysis
MH  - Trastuzumab
RF  - 76
EDAT- 2008/04/01 09:00
MHDA- 2009/01/30 09:00
CRDT- 2008/04/01 09:00
PHST- 2007/11/03 00:00 [received]
PHST- 2008/02/15 00:00 [revised]
PHST- 2008/02/20 00:00 [accepted]
PHST- 2008/04/01 09:00 [pubmed]
PHST- 2009/01/30 09:00 [medline]
PHST- 2008/04/01 09:00 [entrez]
AID - S0304-419X(08)00006-1 [pii]
AID - 10.1016/j.bbcan.2008.02.003 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2008 Dec;1786(2):105-13. doi: 10.1016/j.bbcan.2008.02.003. 
      Epub 2008 Mar 4.